Abstract
Folic acid intake has increased to high levels in many countries, raising concerns about possible adverse effects, including disturbances to energy and lipid metabolism. Our aim was to investigate the effects of excess folic acid (EFA) intake compared to adequate folic acid (AFA) intake on metabolic health in a rodent model. We conducted these investigations in the setting of either a 15% energy low fat (LF) diet or 60% energy high fat (HF) diet. There was no difference in weight gain, fat mass, or glucose tolerance in EFA-fed rats compared to AFA-fed rats when they were fed a LF diet. However, rats fed EFA in combination with a HF diet had significantly greater weight gain and fat mass compared to rats fed AFA (p < 0.05). Gene expression analysis showed increased mRNA levels of peroxisome proliferator-activated receptor γ (PPARγ) and some of its target genes in adipose tissue of high fat-excess folic acid (HF-EFA) fed rats. Inflammation was increased in HF-EFA fed rats, associated with impaired glucose tolerance compared to high fat-adequate folic acid (HF-AFA) fed rats (p < 0.05). In addition, folic acid induced PPARγ expression and triglyceride accumulation in 3T3-L1 cells. Our results suggest that excess folic acid may exacerbate weight gain, fat accumulation, and inflammation caused by consumption of a HF diet.
Highlights
The metabolic syndrome, which encompasses excess abdominal adiposity, insulin resistance, dyslipidaemia, and hypertension, represents the largest public health challenge in developed countries [1]
Glucose tolerance tests showed no difference in rate of glucose clearance between low fat (LF)-adequate folic acid (AFA) and LF-excess folic acid (EFA) fed rats (Figure 1D,E)
Glucose tolerance tests showed no difference in rate of glucose clearance between LF‐AFA and LF‐EFA fed
Summary
The metabolic syndrome, which encompasses excess abdominal adiposity, insulin resistance, dyslipidaemia, and hypertension, represents the largest public health challenge in developed countries [1]. The rise in metabolic syndrome prevalence in recent decades has been mirrored by changes in dietary patterns, reflecting increased nutrient availability [2]. Folates are a family of structurally-similar compounds involved in the transfer of one-carbon units for the production of nucleotides used in DNA synthesis; for the methylation of a variety of biological substrates; and for cell division [4].
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